The long term objective is to define the synaptic relationships among brain stem respiratory neurons and their contribution to the generation and coordination of discharge patterns which underlie the rhythmic respiratory drive to motor neurons. Planned experiments address three hypotheses. 1. Redundant, ccomplementary synaptic interactions among spatially distributed neurons with demonstrable functional links to respiratory motor and premotor neurons contribute to both the development and termination of each phase of breathing. 2. The strength of synaptic coupling among some classes of co-active respiratory neurons varies with the gating actions of other brain stem neurons during each phase of breathing. These modulatory processes help to regulate phase durations. 3. Neurons located in one region of the brain stem capable of independent rhythmogenesis are linked by multiple coordinating mechanisms to cells in each other such region. Experiments will be performed with anesthetized or decerebrate, paralyzed, bilaterally vagotomized, ventilated cats. Three independently controlled arrays of extracellular tungsten and multi-barrel pipette electrodes (total=12) will be used to monitor simultaneously respiratory neurons in the medulla (including the dorsal and ventral respiratry groups) and/or pons (including the rostral respiratory group or "pneumotaxic area"). Microiontophoresis of amino acids, peptides, or transmitter antagonists will be used to enhance or suppress the activities of selected cells. Neurons with spinal or vagal projections will be identified using antidromic stimulation methods. Functional interactions will be detected and evaluated using cross-correlational and spike triggered averaging methods, a "gravitational clustering" method, pharmacological manipulations of putative driver and modulatory neurons, and network simulations. The results of these experiments will provide insights into the central neural mechanisms underlying the breathing rhythm and the remarkable ability of the system to tolerate insults of various origins.